Journal of Molecular Cell Biology最新文献_第5页

Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells. Rbfox1 控制着心肌细胞中局灶粘附基因的替代剪接。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjae003

Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn

{"title":"Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells.","authors":"Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn","doi":"10.1093/jmcb/mjae003","DOIUrl":"10.1093/jmcb/mjae003","url":null,"abstract":"Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants. However, it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing. Hence, we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail. By using a combination of in silico target prediction and in-cell validation, we identified several focal adhesion proteins as alternative splicing targets of Rbfox1. We focused on the alternative splicing patterns of vinculin (metavinculin isoform) and paxillin (extended paxillin isoform) and identified both as potential Rbfox1 targets. Minigene analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the introns. Focal adhesions play an important role in the cardiac muscle context, since they mainly influence cell shape, cytoskeletal organization, and cell-matrix association. Our data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology, cytoskeletal organization, and multinuclearity after differentiation, which might be due to changes in alternative splicing of focal adhesion proteins. Hence, our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells, which might contribute to heart disease progression, where downregulation of Rbfox1 is frequently observed.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms. 病理相关醛糖和环境醛通过甲酰基介导的机制引起纤毛的破坏。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad079

Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou

{"title":"Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms.","authors":"Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou","doi":"10.1093/jmcb/mjad079","DOIUrl":"10.1093/jmcb/mjad079","url":null,"abstract":"Carbohydrate metabolism disorders (CMDs), such as diabetes, galactosemia, and mannosidosis, cause ciliopathy-like multiorgan defects. However, the mechanistic link of cilia to CMD complications is still poorly understood. Herein, we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols. Moreover, environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups. Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane, which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly. In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella. These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The next decade of SET: from an oncoprotein to beyond. SET 的下一个十年：从肿瘤蛋白到超越。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad082

Han Yao, Meng Zhang, Donglai Wang

引用次数: 0

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway. 通过抑制表皮生长因子受体-Stat3/Akt通路，消耗Gsdma1/2/3可减轻PMA诱导的表皮增生。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad080

Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin

{"title":"Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway.","authors":"Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin","doi":"10.1093/jmcb/mjad080","DOIUrl":"10.1093/jmcb/mjad080","url":null,"abstract":"Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice do not show any visible phenotypes in skin and hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. These mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to the decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell analysis defines LGALS1 + fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma. 单细胞分析确定了促进肝内胆管癌增殖和迁移的 LGALS1 + 成纤维细胞。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-06-11 DOI: 10.1093/jmcb/mjae023

Qiqi Cao, Jinxian Yang, Lixuan Jiang, Zhao Yang, Zhecai Fan, Shuzhen Chen, Sibo Zhu, Lei Yin, Hongyang Wang, Wen Wen

{"title":"Single-cell analysis defines LGALS1 + fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.","authors":"Qiqi Cao, Jinxian Yang, Lixuan Jiang, Zhao Yang, Zhecai Fan, Shuzhen Chen, Sibo Zhu, Lei Yin, Hongyang Wang, Wen Wen","doi":"10.1093/jmcb/mjae023","DOIUrl":"https://doi.org/10.1093/jmcb/mjae023","url":null,"abstract":"The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity of ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified ten major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. The higher amount of LGALS1 + fibroblasts were associated with poorer overall survival in ICC patients. LGALS1 + fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and β-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts. Our work will further the understanding of the intratumor heterogeneity of ICC and provide novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZW10: an emerging orchestrator of organelle dynamics during the cell division cycle. ZW10：细胞分裂周期中细胞器动力学的新兴协调者

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-06-03 DOI: 10.1093/jmcb/mjae026

Sm Faysal Bellah, Fengrui Yang, Fangyuan Xiong, Zhen Dou, Xuebiao Yao, Xing Liu

引用次数: 0

Extracellular vesicles in cancer: Golden goose or trojan horse 癌症中的细胞外囊泡：金鹅还是特洛伊木马

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-25 DOI: 10.1093/jmcb/mjae025

Tao Han, Qian Hao, Tengfei Chao, Qinggang Sun, Yitian Chen, Bo Gao, Liping Guan, Wenjie Ren, Xiang Zhou

引用次数: 0

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis. SPIN1 通过其 IDR 的相分离促进了组蛋白甲基化读出和肿瘤发生。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-22 DOI: 10.1093/jmcb/mjae024

Yukun Wang, Yuhan Chen, Mengyao Li, Jiayue Wang, Yuhan Jiang, Rong Xie, Yifeng Zhang, Zhihua Li, Zhenzhen Yan, Chen Wu

{"title":"Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.","authors":"Yukun Wang, Yuhan Chen, Mengyao Li, Jiayue Wang, Yuhan Jiang, Rong Xie, Yifeng Zhang, Zhihua Li, Zhenzhen Yan, Chen Wu","doi":"10.1093/jmcb/mjae024","DOIUrl":"https://doi.org/10.1093/jmcb/mjae024","url":null,"abstract":"Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production. CCT6A通过抑制HIF-1α介导的乳酸生成减轻肺纤维化。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-17 DOI: 10.1093/jmcb/mjae021

Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu

{"title":"CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production.","authors":"Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu","doi":"10.1093/jmcb/mjae021","DOIUrl":"https://doi.org/10.1093/jmcb/mjae021","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, and recent studies indicate that lactate plays a significant role in promoting the progression of the disease. Nevertheless, the mechanism by which lactate metabolism is regulated and the downstream effects remain unclear. The molecular chaperone CCT6A performs multiple functions in a variety of biological processes. Our research has identified a potential association between CCT6A and serum lactate levels in IPF patients. Herein, we found that CCT6A was highly expressed in type 2 alveolar epithelial cells (AEC2s) of fibrotic lung tissues and correlated with disease severity. Lactate increases the accumulation of lipid droplets in epithelial cells. CCT6A inhibits lipid synthesis by blocking the production of lactate in AEC2s and alleviates bleomycin-induced pulmonary fibrosis in mice. In addition, our results revealed that CCT6A blocks HIF-1α-mediated lactate production by driving the VHL-dependent ubiquitination and degradation of HIF-1α and further inhibits lipid accumulation in fibrotic lungs. In conclusion, we propose that there is a pivotal regulatory role of CCT6A in lactate metabolism in pulmonary fibrosis, and strategies aimed at targeting these key molecules could represent potential therapeutic approaches for pulmonary fibrosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-specific nucleases in genome dynamics and strategies for targeting cancers. 基因组动态中的结构特异性核酸酶和针对癌症的策略。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-07 DOI: 10.1093/jmcb/mjae019

Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen

{"title":"Structure-specific nucleases in genome dynamics and strategies for targeting cancers.","authors":"Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen","doi":"10.1093/jmcb/mjae019","DOIUrl":"https://doi.org/10.1093/jmcb/mjae019","url":null,"abstract":"Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogeneous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0